Neurological Sciences (2019) 40:603–609 https://doi.org/10.1007/s10072-018-3688-4 ORIGINAL ARTICLE Incidence study of Guillain-Barré syndrome in the province of Ferrara, Northern Italy, between 2003 and 2017. A 40-year follow-up Enrico Granieri1 & Nico Golfrè Andreasi1 & Paolo De Martin1 & Vittorio Govoni1 & Massimiliano Castellazzi1 & Edward Cesnik1 & Maura Pugliatti1 & Ilaria Casetta1 Received: 11 September 2018 /Accepted: 14 December 2018 /Published online: 7 January 2019 # Fondazione Società Italiana di Neurologia 2019 Abstract Background Guillain-Barré syndrome (GBS) is an acute/subacute autoimmune inflammatory polyradiculoneuropathy. Previous epidemiological studies carried out in the province of Ferrara, Italy, from 1981 to 2002 indicated that GBS incidence had tendency of increase in the period considered. Objectives We aimed at updating the epidemiology of GBS in the years 2003–2017andcarryingontheworkstartedinthe1980s. Methods We conducted an incidence study, by adopting a complete enumeration approach. Cases were identified from admin- istrative, medical records, and database of the Ferrara Hospital and other provincial structures of the study area. Case ascertain- ment and definition are analogous to those adopted in previous surveys. Results In the period 1 January 2003 to 31 December 2017, 73 patients living in the province of Ferrara (mean population 353,142) were found to be new cases of GBS fulfilling the NINCDS criteria. Male/female ratio 1.15. The mean incidence rate was 1.38 per 100,000 (95% CI 1.08–1.74), 1.54 per 100,000 for men and 1.23 per 100,000 for women, a nonsignificant difference. During the period considered, the rates had slow increase or mild decrease, without nonsignificant difference. The highest rates were observed for the age groups 70–79 years for both sexes. A half of patients reported infectious events in the weeks before the onset of symptoms. Conclusion In line with many epidemiological data, in the whole period 2003–2017, we observed a trend towards increase or decrease in incidence and periods of relative stability. Similar temporal heterogeneity with the comparison to our previous works was found. Keywords Guillain-Barré syndrome . Epidemiology . Incidence . Ferrara . Italy Introduction two thirds of cases with a previous infection of the upper respiratory tract or gastrointestinal system (usually 4 weeks Guillain-Barré syndrome (GBS) is an acute-subacute autoim- prior to the onset of GBS symptoms) [2]. mune inflammatory polyradiculoneuropathy [1]. The patho- GBS is characterized by an ascending flaccid paralysis, physiology of the disease is intimately correlated for at least with reduction or absence of muscle reflexes; the paralysis * Enrico Granieri Edward Cesnik [email protected] [email protected] Nico Golfrè Andreasi Maura Pugliatti [email protected] [email protected] Paolo De Martin Ilaria Casetta [email protected] [email protected] Vittorio Govoni [email protected] 1 Department of Biomedical and Specialty-Surgical Sciences, Massimiliano Castellazzi Section of Neurology, Psychology and Psychiatry, University of [email protected] Ferrara, Via Aldo Moro 8, 44124 Cona, Ferrara, Italy 604 Neurol Sci (2019) 40:603–609 could develop acutely, within few days, or subacutely, within Materials and methods weeks [3]. The muscle weakness reaches a plateau and then shows a spontaneous and mostly complete recovery. In about Study population and area 15% of cases however, even with an adequate immunomod- ulatory treatment, the outcome is poor after 1 year of follow- The province of Ferrara is located in Emilia Romagna, a re- up. In a considerable number of cases (20–30%), respiratory gion in north-eastern Italy; the population is mixed but the vast muscle is severely involved and patients need mechanical majority is Caucasian. It covers a surface of 2632 km2 and the ventilation, an event considered to be an important risk factor mean population density is 133 inhabitants/km2. The geo- of poor outcome [3, 4]. graphical, political, and socioeconomical characteristics and GBS is now the most common cause of acute or subacute medical facilities of the study area were described in detail in flaccid paralysis in the western countries, after the eradication previous epidemiological studies (Fig. 1)[7–9]. The standard of poliomyelitis [5]. of living is on the average high; in the last decades, the level of The incidence of GBS has been worldwide and extensively medical organization has also become more efficient. Health studied, estimating a mean incidence of 1–2 cases per 100,000, care is free for all residents, whether Italian citizens or not. The but with a relatively wide range of 0.16 to 4.0 per 100,000 public health system allows a wide availability of data, from population [3, 4, 6]. This considerable difference could be due both paper and computerized administrative records. to a factual variable incidence across different world regions, Ferrara University Hospital provides first- and second- but also to methodological differences in case definition and level medical and surgical care and comprises two neurolog- ascertainment, and in the size of the population studied. ical units with day-hospital, outpatient services, relying on The results of previous epidemiological studies carried out in clinical neurophysiology, neuroimaging (MRI), laboratory fa- the province of Ferrara, Northern Italy, performed by this same cilities for cerebrospinal fluid (CSF) analyses, and a research group from 1981 to 2002 indicated that GBS risk had a neurorehabilitation unit. Neurological patients of the province tendency to increase in the period considered, with mean rates of Ferrara and neighboring areas are routinely referred to the which vary from 1.26 per 100,000 over the years 1981–1987 [7] Neurological Clinic and Unit and the Motor Rehabilitation of to 1.87 per 100,000 in the years 1988–1993 [8] and 1.97 per Ferrara University Hospital. Other three hospitals in the prov- 100,000 over the years 1994–2001 [9]. Therefore, our intent ince have services of neurology, neurophysiology, and neuro- was to update the GBS incidence estimates in the same area, imaging which all have a strict connection with the services of considering its favorable conditions, namely, the stable availabil- the Neurological Units of the Ferrara University Hospital. All ity and quality of medical services and the greater experience in the hospitals of the province make use of the neurochemistry the epidemiological field of our research group over time. laboratory located in Sant’Anna University Hospital, Ferrara. Fig. 1 Province of Ferrara. Area of investigation. Borders of the various public health districts are indicated. (1 = Ferrara; 2 = Comacchio; 3 = Portomaggiore; 4 = Copparo; 5 = Cento; • neurological centers) Neurol Sci (2019) 40:603–609 605 The local authority service of the province (Azienda as percentages or ratios, and comparisons were made by the Sanitaria Locale, ASL) supplies domiciliary assistance such chi-square test. A two-tailed probability distribution at 95% as medical assistance, nursing homes for bedridden patients, was chosen and p was set at < 0.05. motor rehabilitation, and occupational therapy. We studied the incidence of GBS on the population living in the province of Ferrara between January 1, 2003, and Results December 31, 2017. In that period, a mean of 353,142 people per year lived in the province. A total of 164 medical records were found using the case selection method described above; of these, 43 were excluded Case selection because the patients were not living in the province of Ferrara; out of the other 121 records, in the whole period 1 January We adopted the same methodological approach of previous 2003 to 31 December 2017, 73 cases (39 men and 34 women) studies [7–9], in order to have reliable comparisons, even if were actually found to be new cases of GBS fulfilling the a larger population was considered in this study compared to NINCDS criteria. The male/female ratio was 1.15. Among previous papers. We searched the health system administrative the examined records, no patients diagnosed with Miller- database for patients who were discharged from hospital with Fisher syndrome were found. Three patients (4.11%) had the a primary or secondary diagnosis of Bacute infectious axonal subtypes; the other 70 subjects had classical acute in- polyneuropathy^ codified by the code 357.0 of the flammatory demyelinating polyneuropathy (AIDP). International Classification of Diseases 9th edition (ICD-9); The mean age at onset was 52.57 years (range 2–85 years, then, we excluded the patients who were not resident in the SD 17.2), 53.62 years for men (range 8–84 years, SD 17.7) province of Ferrara. and 48.29 years for women (range 2–85 years, SD 16.8), a Moreover, we could screen the database of medical records nonsignificant gender difference. of the main hospitals of the bordering provinces and regions, In 2013, we only found one GBS case, while the maximum with particular regards to the Veneto and Romagna regions number was 9 cases in 2016, with a mean of 4.87 cases/ with the aim to find possible GBS patients residing in the 100,000/year (Table 1). Ferrara Province at the incidence period. No patient residing The mean incidence crude rate during the study period was in the province of Ferrara was found. 1.38 per 100,000/year (95% CI 1.08–1.74), 1.54 per 100,000 Many patients have acute infectious polyneuropathy only for men (95% CI 1.09–2.11) and 1.23 per 100,000 for women as a secondary diagnosis; all the data of these patients were (95% CI 0.85–1.72), a nonsignificant gender difference. reviewed, and those found to have only sequelae of a previous The incidence rates adjusted to the Italian population were history of GBS were also excluded. Two patients showed a 1.33 per 100,000 (95% CI 1.04–1.68), 1.49 per 100,000 (95% replication of the attack, 3 and 5 months after the first relapse; CI 1.6–2.04) for men and 1.30 per 100,000 (95% CI 0.90– in the selection of incidence cases, they were considered only 1.82) for women, respectively.